Aloe-emodin induced in vitro G2/M arrest of cell cycle in human promyelocytic leukemia HL-60 cells
Introduction
Leukemia of human blood has poor therapy. Therapeutic approaches for human leukemia include radiation treatment, hyperthermia and chemotherapy. However, conventional strategies for treatment of human leukemia are not yet satisfactory. Some of the well known anticancer drugs are known to induce apoptosis via the inhibition of topoisomerase II (Kaufmann, 1989; Walker et al., 1991; Ling et al., 1993; Stevnsner and Bohr, 1993). Cell apoptosis is characterised and involved by a series of typical morphological events, for example shrinkage of the cell, DNA fragmentation, fragmentation into membrane-bound apoptotic bodies and rapid phagocytosis by neighbouring cells (Kerr et al., 1972). Many epidemiological studies showed that protective effects of vegetables and fruits against cancer reduced risks of cardiovascular disease associated with high intakes of dietary antioxidants (Hollman and Katan, 1996).
Sennosides are the major important constituents of senna extracts from many plants, which can be transformed by bacterial enzymes to produce the sennins and anthrones before following oxidation to form anthraquinones outside the reductive atmosphere of the large intestine in humans (Kobashi et al., 1980). The sennidins can undergo further decomposition to form the aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-9,10-anthracenedione) which is a hydroxyanthraquinone in blood. From the in vitro incubation tests, it showed that aloe-emodin could induce mutagenic and genotoxic activity (Westendorf et al., 1990). But it is also reported that aloe-emodin did not induce cytotoxicity in L 1210 leukemia cells (Driscoll, 1974). Other investigators also pointed out that at high concentrations, aloe-emodin did induce cytotoxicity for erythroleukemia cell lines. The important point is that aloe-emodin had been reported to be a new type of anticancer agent with selective activity against neuroectodermal tumors (Pecere et al., 2000) and induced apoptosis in human lung squamous cell carcinoma (Lee et al., 2001) and human hepatoma cell lines (Kuo et al., 2002). So far, there is no available information which addresses the effects of aloe-emodin on apoptosis in human leukemia cells (HL-60). Thus, the present study was performed to determine whether aloe-emodin could induce apoptosis in human leukemia cells.
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Chemicals and reagents
Aloe-emodin, trypan blue, Tris–HCl, triton X-100, propidium iodide (PI), ribonuclease A were obtained from Sigma Chemical Co. (St. Louis, MO, USA). Dimethyl sulfoxide (DMSO), potassium phosphates, and TE buffer (10 mM Tris–HCl, 1 mM EDTA, PH 7.6) were purchased from Merck Co (Darmstadt, Germany). RNase was obtained from BD Biosciences Clontech (Palo Alto, CA, USA). RPMI 1640 medium, fetal bovine serum, penicillin-streptomycin and l-glutamine were obtained from Gibco BRL (Grand Island, NY, USA).
Effects of various concentrations of aloe-emodin on cell viability of human leukemia HL-60 cells
The results from PI stain experiments indicated that <2% of HL-60 (human leukemia cells) were stained when they were incubated in RPMI 1640 medium containing 10% FBS. In contrast, in the presence of aloe-emodin (5–25 μM), the cells were increased by staining after the time and concentration increased for HL-60 cells, suggesting that aloe-emodin induced antiproliferative activity in HL-60 (Fig. 1). Further increase in the concentration of aloe-emodin resulted in greater decrease in the viable
Discussion
Leukemia is one of the most deadliest cancers in the world. Chemoprevention is a promising way to stop the development of such cancers. Large numbers of minor dietary components has been reported to inhibit various stages of carcinogenesis (Donaldson et al., 1994). Aloe-emodin has been demonstrated to be one of such chemopreventive agents but the underlying mechanisms are not well understood for HL-60 cells. Here, we have demonstrated that the possible role of the aloe-emodin was (i) to
Acknowledgments
This work was supported by grant NSC89-2745-P-039-001 from the National Science Council of Taiwan.
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2023, Spectrochimica Acta - Part A: Molecular and Biomolecular SpectroscopyCitation Excerpt :In vivo studies have shown that orally administered Barbaloin is poorly absorbed, but metabolized by intestinal micro flora into Aloe-emodin [19], known as the reduced form of Barbaloin, which is very stable and more readily absorbed [20 3]. This anthraquinone has demonstrated efficacy in several cancer types, including human lung carcinoma [21 22], hepatoma [23 24], breast [25 26], colon carcinoma [27 28] and leukemia [29 30]. Aloe-emodin was also reported to induce apoptosis in human gastric carcinoma cells [31], lung carcinoma cells [21] and hepatoma cells [24 23].
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